DESCRIPTION: (Principal Investigator's Abstract): Vanadium is increasingly a source of possible toxic effects through the use of fossil fuels and its incorporation into metal alloys. Vanadium in the form of vanadate has been shown to have a number of insulin-mimetic properties when given acutely in vitro. However, the effects of chronic administration on insulin sensitive tissues in vivo is much less well studied. Therefore, the overall purpose of this proposal is to examine the effects of vanadium on insulin-sensitive activities at its target cell sites. The specific objectives are: 1) to determine if vanadate or vanadyl is preferentially accumulated and retained in tissues with insulin-sensitive glucose transport systems; 2) to determine if vanadium alters insulin receptor numbers, binding, or function; 3) to determine if vanadium has effects on insulin-stimulated activities in target tissues; and 4) to determine if vanadium affects insulin metabolism. Rats will be given vanadium, as sodium orthvanadate or vanadyl sulfate, in a liquid diet and a number of insulin-sensitive activities of target tissues measured and compared to control animals. Specifically, various organs will be harvested and the vanadium content determined by neutron activation analysis. Hepatocytes and adipocytes will be isolated from animals and insulin binding analyzed by Scatchard plots. Receptor function will be assessed by assaying its tyrosine kinase activity. Isolated hepatocytes will be assayed for the insulin-sensitive activities of: amino acid transport, inhibition of protein degradation, and glucose incorporation in glycogen. Isolated adipocytes will be assayed for the insulin-sensitive activities of: glucose uptake, glucose incorporation into lipids, glucose oxidation, and anti-lipolysis. Finally, insulin degradation will be studied in perfused liver and isolated hepatocytes to determine if vanadium alters its metabolism. Those studies will allow determination of the effect of vanadium on insulin target tissue and begin analysis of its mechanisms of action.